Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis.
Di-n-butyl-(2,6-difluorobenzohydroxamato)Tin(IV) (DBDFT), a potential antitumor agent against malignancies, exhibited high activities both in vitro and in vivo. Flow cytometric analysis showed that treatment with DBDFT against Human Gastric Carcinoma (SGC-7901) cells induced a concentration and time...
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Public Library of Science (PLoS)
2014-01-01
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Online Access: | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24643073/?tool=EBI |
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author | Li Yunlan Zheng Juan Li Qingshan |
author_facet | Li Yunlan Zheng Juan Li Qingshan |
author_sort | Li Yunlan |
collection | DOAJ |
description | Di-n-butyl-(2,6-difluorobenzohydroxamato)Tin(IV) (DBDFT), a potential antitumor agent against malignancies, exhibited high activities both in vitro and in vivo. Flow cytometric analysis showed that treatment with DBDFT against Human Gastric Carcinoma (SGC-7901) cells induced a concentration and time-dependent cell accumulation in the G2/M phase of the cell cycle with a parallel depletion of the percentage of cells in G0/G1, the cell apoptosis was observed by characteristic morphological changes and AnnexinV/PI dual-immunofluorescence staining. Fluorescence quantitative FQ- PCR and western blot results showed that G2/M-phase arrest was correlated with up-regulation of cyclin dependent kinase inhibitor p21, Chk2 and CyclinB1, whereas the expressions of other G2/M regulatory check-point protein, Cdc2, and feedback loop protein Cdc25C were obviously down-regulated in a p53-independent manner after the SGC-7901 cells were treated with DBDFT (2.5, 5.0, 7.5 µmol·L(-1)) compared with the control. Furthermore, the up-regulation of Bax and down-regulation of Bcl-2 as well as the activation of caspase-3 were observed, which indicated that DBDFT treatment triggered the mitochondrial apoptotic pathway with an increase of Bax/Bcl-2 ratios, resulting in mitochondrial membrane potential loss and caspase-9 activation in DBDFT treated SGC-7901 cells. In summary, the results illustrated the involvement of multiple signaling pathways targeted by DBDFT in mediating G2/M cell cycle arrest and apoptosis in SGC-7901 cells, which suggested that DBDFT might have therapeutic potential against gastric carcinoma as an effective compound. |
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spelling | doaj.art-4dd27aca695e4ce08332daad7cd18c852022-12-21T23:16:58ZengPublic Library of Science (PLoS)PLoS ONE1932-62032014-01-0193e9079310.1371/journal.pone.0090793Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis.Li YunlanZheng JuanLi QingshanDi-n-butyl-(2,6-difluorobenzohydroxamato)Tin(IV) (DBDFT), a potential antitumor agent against malignancies, exhibited high activities both in vitro and in vivo. Flow cytometric analysis showed that treatment with DBDFT against Human Gastric Carcinoma (SGC-7901) cells induced a concentration and time-dependent cell accumulation in the G2/M phase of the cell cycle with a parallel depletion of the percentage of cells in G0/G1, the cell apoptosis was observed by characteristic morphological changes and AnnexinV/PI dual-immunofluorescence staining. Fluorescence quantitative FQ- PCR and western blot results showed that G2/M-phase arrest was correlated with up-regulation of cyclin dependent kinase inhibitor p21, Chk2 and CyclinB1, whereas the expressions of other G2/M regulatory check-point protein, Cdc2, and feedback loop protein Cdc25C were obviously down-regulated in a p53-independent manner after the SGC-7901 cells were treated with DBDFT (2.5, 5.0, 7.5 µmol·L(-1)) compared with the control. Furthermore, the up-regulation of Bax and down-regulation of Bcl-2 as well as the activation of caspase-3 were observed, which indicated that DBDFT treatment triggered the mitochondrial apoptotic pathway with an increase of Bax/Bcl-2 ratios, resulting in mitochondrial membrane potential loss and caspase-9 activation in DBDFT treated SGC-7901 cells. In summary, the results illustrated the involvement of multiple signaling pathways targeted by DBDFT in mediating G2/M cell cycle arrest and apoptosis in SGC-7901 cells, which suggested that DBDFT might have therapeutic potential against gastric carcinoma as an effective compound.https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24643073/?tool=EBI |
spellingShingle | Li Yunlan Zheng Juan Li Qingshan Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis. PLoS ONE |
title | Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis. |
title_full | Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis. |
title_fullStr | Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis. |
title_full_unstemmed | Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis. |
title_short | Antitumor activity of di-n-butyl-(2,6-difluorobenzohydroxamato)tin(IV) against human gastric carcinoma SGC-7901 cells via G2/M cell cycle arrest and cell apoptosis. |
title_sort | antitumor activity of di n butyl 2 6 difluorobenzohydroxamato tin iv against human gastric carcinoma sgc 7901 cells via g2 m cell cycle arrest and cell apoptosis |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/pmid/24643073/?tool=EBI |
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